Instructions for vosoritide

1. Name:Voxzogo, vosoritide, vosoritide ( transliteration)

2. Indications:

Voxzogo (vosoritide) promotes linear growth in children with achondroplasia with open epiphyses. This indication received accelerated approval based on improvement in annualized growth rate, and continued approval for this indication may be contingent on verification and characterization of clinical benefit in confirmatory trials.

3. Usage and dosage:

1. Before treatment: To reduce the risk of hypotension and its related signs and symptoms, patients should eat enough before treatment with Voxzogo and drink approximately 240 to 300 ml of fluid one hour before dosing.

2. Recommended dosage: The recommended dosage of Voxzogo is based on the patient's actual weight and is administered by subcutaneous injection once a day; the volume of Voxzogo to be administered (injection volume) is based on the patient's actual weight and the concentration of reconstituted Voxzogo (0.8 mg/mL or 2 mg/mL). If possible, inject Voxzogo at about the same time each day.

The actual weight of the patient is 3kg, the dose is 0.096mg, and the injection volume is 0.12mL; the dose for the patient weighing 4kg is 0.12mg, the injection volume is 0.15mL; the dose for the patient weighing 5kg is 0.16 mg, the injection volume is 0.2mL; the dosage for people weighing 6-7kg is 0.2mg, the injection volume is 0.25mL; the dosage for people weighing 8-11kg is 0.24mg, the injection volume is 0.3mL; the dosage for people weighing 12-16kg is 0.28mg, the injection volume is 0.35mL; the dose for those weighing 17-21kg is 0.32mg, the injection volume is 0.4mL; the dose for those weighing 22-32kg is 0.4mg, the injection volume is 0.5mL; the dose for those weighing 33-43kg is 0.5mg, the injection volume is 0.25m L; the dose for those weighing 44-59kg is 0.6mg, and the injection volume is 0.3mL; the dose for those weighing 60-89kg is 0.7mg, the injection volume is 0.35mL; the dose for those weighing ≥90kg is 0.8mg, and the injection volume is 0.4mL.

3. Missed dose: If you miss a doseVoxzogo can be administered within 12 hours of the scheduled dosing time. After 12 hours have elapsed, skip the missed dose and take the next daily dose according to the usual dosing schedule.

4. Medication monitoring: Regularly monitor and evaluate the patient's weight, growth and physical development every 3 to 6 months. Adjust dosage based on patient's actual weight. After confirmation of the lack of further growth potential (indicated by epiphyseal closure), permanently discontinue use of Voxzogo.

4. Adverse reactions:

In clinical studies of Voxzogo, common adverse reactions included injection site reactions (redness, itching, swelling, bruising, rash, hives, pain), high blood alkaline phosphatase levels, joint pain, vomiting, decreased blood pressure, and gastroenteritis.

5. Supply and storage:

For InjectionVoxzogo is a white to yellow lyophilized powder for reconstitution and is available in co-packaged form. Keep Voxzogo vials and prefilled diluent syringes refrigerated at 2°C to 8°C (36°F to 46°F). Do not freeze. Please store in original packaging to protect from light.

Voxzogo can be stored at room temperature 20°C to 25°C (68°F to 77°F); allowed to travel within 15°C to 30°C (59°F to 86°F) for 90 days. After storing at room temperature, do not return Voxzogo to the refrigerator. After reconstitution, VOXZOGO can be stored in vials at room temperature 20°C to 25°C (68°F to 77°F) for up to 3 hours.

6. Mechanism of action:

In patients with achondroplasia, endochondral bone growth is negatively regulated due to functional mutations in fibroblast growth factor receptor3 (FGFR3). Voxzogo's component vosoritide binds to natriuretic peptide receptor-B (NPR-B) to antagonize FGFR3 downstream signaling by inhibiting extracellular signal-regulated kinases 1 and 2 (ERK1/2) in the mitogen-activated protein kinase (MAPK) pathway at the level of rapidly accelerating fibrosarcoma serine/threonine protein kinase (RAF-1). Therefore, vosoritide, like CNP, acts as a positive regulator of endochondral bone growth as it promotes chondrocyte proliferation and differentiation.

In animal models with open growth plates, administration of vosoritide resulted in promotion of chondrocyte proliferation and differentiation, which resulted in widening of the growth plate and subsequent increase in bone growth. In mouse models of FGFR3-related chondrodysplasia, partial or complete normalization of the dwarfism phenotype is observed.

8. Notes:

1. Risk of hypotension: A transient decrease in blood pressure was observed in clinical studies of Voxzogo. Subjects with severe heart or blood vessel disease and patients taking antihypertensive medications were excluded from Voxzogo clinical trials. To reduce the risk of a drop in blood pressure and related symptoms (dizziness, fatigue and/or nausea), instruct patients to stay well hydrated and eat enough food before taking Voxzogo.